Medical imaging is perhaps the most important crossover area in medical engineering – it’s generally accepted that it was imaging that convinced the medical world that engineers could have an important contribution to make. But when it comes to looking at the basic unit of biology, the cell, engineering hasn’t produced many advances. The optical microscope is still the instrument used to look at cells and, although this has been refined over the years, it has had the same basic concept and design since the days of Robert Hooke in the 17th century.

Researchers from the Gray Institute for Radiation Oncology and Biology, part of Oxford University’s medical school, have been working on a cell-imaging system that takes a different tack from the classic microscope. Smaller and cheaper than a microscope, it allows scientists to follow the fate of cells as they divide, grow and die, making it useful for assessing the effectiveness of cancer therapy or other medicines and treatments, as well as many other applications, and it does all this without using a single lens.

The project started with a £2.3m grant from Research Councils UK to a group including the Gray Institute, to find a low-cost technique to identify the presence of cells and to monitor their status and movement, all using visible light. The problem here is that cells are transparent; although microscopes can see them, it’s very difficult to miniaturise a microscope. The Gray team, led by Borivoj (Boris) Vojnovic, decided to use a different optical property. Microscopes detect things by looking at reflected or absorbed light. But light passes through cells and as it does so it interacts with the various structures of the cell – it is diffracted. The team used this property to develop a device, known as CyMap, which uses the diffraction patterns made by cells to study them.

These are not images in the sense of what you’d see looking down a microscope,’ Vojnovic said, ‘but they are images in the sense that they are 2D maps of brightness. This map, this image, is characteristic of cells of different dimensions, so it can distinguish between cells that are physically different, such as when they are at different points in their lifecycle.’

CyMap is for use with cells that are being cultured, rather than on cell samples taken from people or animals. It uses a small light source, around the size of the cells, to illuminate the sample, which throws the diffraction pattern onto an optical sensor, a charge-coupled device (CCD) similar to those used in digital cameras. ‘In the original project, we used lasers as the light source – we had reasons for doing that, which were connected with other aspects of the project – but we screened them off with pinholes so the diameter of the light source was about 40-50 m,’ explained Iestyn Pope, a research scientist working with Vojnovic at the Gray Institute. ‘Now we’re using a resonant cavity LED, which has a closely confined emission area, giving us a light-source size of about 60 m.’

CyMap doesn’t use any optical components. ‘No lenses,’ Vojnovic said. ‘The cell itself is the lens and there is no focusing required.’ This means that it’s much cheaper than a microscope. ‘We’re using it to look at the response of mammalian cells to radiation,’ he said, ‘and conventionally you’d do that by taking a bunch of cells and irradiating them and then counting which ones are alive and which are dead. You could argue you could do that with a conventional microscope, but if you’d spent hundreds of thousands of pounds on one, the last thing you’d want to do is irradiate it. This is a more disposable technology, but it still gives us the capability we need; we can look at the fate of individual cells as a function of time.’

There are many other applications, Vojnovic explained, and these are currently being studied by the Gray Institute’s commercial partner, Cancer Research Technologies. ‘It comes into its own when it’s used for larger-scale applications, and one obvious one is quality control for any system that involves growing cells in incubators,’ he added. As CyMap is both small and cheap and produces a digital image that can be viewed remotely, one unit could be placed under each culture plate or flask. The growing cells could be monitored without removing them from the incubator.

This, Pope said, would be useful when the researchers need to be certain about the lineage of cells, which is particularly important when itcomes to stem-cell experiments. ‘You need to monitor the division of cells and see which progeny go where and do what.’

There are a variety of other possibilities involving cell kinetics, the study of cell development and lifecycles. Examples include wound healing studies, where cells divide and move around; another is a technique used in drug development called a chemotaxis assay, where the growth medium on the culture plate is impregnated with a drug molecule in a gradient, high concentration on one side to low on the other. This indicates how much of a drug is needed to affect the cells. ‘The devices are small and cheap and you could easily have a dozen of them working in parallel,’ Vojnovic said.

Some training and expertise is needed to operate CyMap, and the team has developed software to help researchers follow the position of the cells. ‘The output is a 2D image of a diffraction pattern and it doesn’t take a particularly large amount of skill to recognise it,’ he said. ‘One output is essentially a movie; another type uses image processing routines to produce a set of coordinates that can be displayed on a screen, making the dimension and the path of the cells more clear.’

Runners up

Medical and healthcareThe other shortlisted candidates in this category were:

POLYMER COATINGS TO CONTROL IN-STENT RESTENOSISBiomer/Liverpool UniversityStents — tiny wire cages used as scaffolding to re-open blocked blood vessels — save lives, but they can also lead to further blockages, as the structures can encourage the growth of smooth muscle cells that narrow the vessel. Specialists at Liverpool University have worked with Biomer to develop a test for polymer materials that could be used for stents, to determine whether they inhibit smooth muscle growth and stimulate the development of healthy blood-vessel lining.

DEVELOPMENT OF LARGE BEARING HIP REPLACEMENTSSouthampton University/Finsbury DevelopmentsSouthampton’s bioengineering department has developed a prosthetic hip joint composed from a titanium cup, which can integrate with bone, lined with a thin ceramic insert that acts as a hard-wearing bearing against the head of the femur. The project used techniques from the aerospace industry to optimise the thickness of the ceramic shell, and developed a pre-assembly technique to reduce the risk of the prosthetic coming apart after implantation.

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